This application is for a five year renewal of the Alzheimer's Disease Research Center (ADRC) at the University of Kentucky's Sanders-Brown Center on Aging. The long-term objective is to build on the existing broad-based AD Program to gain an understanding of the pathogenetic mechanisms in AD with the eventual goal of prevention or treatment of the disease. The ADRC has a multidisciplinary program including basic and clinical research, exemplary clinical care and neuropathological activities, satellite clinics for rural and minority subjects, and a broad spectrum of educational and training programs, all of which are responsive to investigators, health care delivery professionals, AD families, and needs of the community, state, and region. The ADRC provides an important resource for and is complemented by two AD program project grants, a major epidemiologic study and other R01 AD grants. The ADRC receives strong support from the University administration and is housed in a building dedicated to aging and AD research. This application consists of five cores, three projects, and two pilot projects. The Administrative Core organizes, coordinates, and supervises all ADRC activities. The Biostatistical and Data Management Core maintains clinical, neuropathologic and research databases and provides statistical expertise in experimental design and data analysis. The Clinical Core evaluates and longitudinally follows AD patients and control subjects for research studies and subsequent postmortem studies. It recruits and follows a large series of normal volunteer control subjects and maintains Satellite Diagnostic and Treatment Clinics for rural and minority subjects in the Appalachian area of eastern Kentucky and in Nashville, Tennessee in conjunction with Vanderbilt/Meharry Medical Schools. The Neuropathology Core provides diagnoses of autopsied AD patients and control subjects for a wide spectrum of research projects and maintains a tissue bank. The Research Training and Information Transfer Core disseminates information about AD to investigators, health care professionals and the lay community, and facilitates research training of investigators and health care professionals. The research projects include the role of excitotoxicity, amyloid beta peptides and oxidative changes in neuron death in AD (Project 1), the role of neuronal insults in cytoskeletal alterations in AD (Project 2), and development of cholinergic neurons for transplantation in AD (Project 3). Pilot Project 1 will investigate the role of S100beta in AD and Pilot 2 will study the substrate of intellectual decline in vascular dementia using magnetic resonance imaging and spectroscopy.